Autoimmune diseases are characterized by immune responses that are directed against self antigens. These responses are maintained by the persistent activation of self-reactive T lymphocytes. T lymphocytes are specifically activated upon recognition of foreign and/or self antigens as a complex with self major histocompatibility complex (MHC) gene products on the surface of antigen-presenting cells (APC).
Systemic lupus erythematosus (SLE) is a chronic, inflammatory, often multisystemic autoimmune disease which can be acute or insidious in onset. SLE is marked by a wide variety of abnormalities, including arthritis and arthralagias, nephritis, central nervous system manifestations, pleurisy, pericarditis, leukopenia or thrombocytopenia, and hemolytic anemia. One of the most serious complications of SLE is lupus nephritis. Renal involvement usually occurs early in the course of the illness and is the leading cause of death in SLE patients.
SLE is a challenging syndrome for medical professionals because its causes remain to be elucidated and further because it has heterogeneous clinical manifestations. Currently, no specific treatment aimed towards the prevention or cure of SLE is available. Despite the extensive research on the mechanisms underlying the induction of SLE, the information on the etiology of the disease is still limited. Diagnosis of SLE is made on the basis of a number of clinical symptoms such as the so-called “butterfly rash,” an erythematous rash which frequently appears on the cheeks of afflicted individuals, crossing the bridge of the nose and becoming more pronounced upon exposure to sunlight; and arthritis which can affect any joint system. However, diagnosis is difficult to verify without appropriate laboratory tests. In this regard, antibodies directed to double-stranded DNA (dsDNA) are diagnostic of SLE and serum titers have long been known to correlate with disease activity in both humans and mice (see, e.g. Pearson et al., J. Immunol. 126:16 (1981)).
Currently, there is no generalized treatment regimen for SLE, although physicians prescribe often prescribe widely immunosuppressive medications such as glucocorticoids. The choice of treatment regimen is typically determined by the individual patient's symptomatology and health status. Consequently, there is a need for broadly applicable treatment regimens, especially for the nephritic manifestations of SLE.